Efficacity and Safety of Tranexamic Acid in Cirrhotic Patients Presenting With Acute Upper Gastrointestinal Bleeding

NCT03023189 | Unknown Phase 4 DMC

• 2 other identifiers: P1509592016-002677-35
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 3

Brief Summary

Upper digestive bleeding. Upper gastrointestinal haemorrhage is a common cause of decompensated cirrhosis and is associated with a high mortality rate among cirrhotic patients. Its leading cause is the rupture of gastro-esophageal varices due to portal hypertension. In cirrhotic patients, the management of acute gastrointestinal haemorrhage is challenging as they often present with coagulation (or haemostasis abnormalities) abnormalities such as hyperfibrinolysis, especially when the cirrhosis is decompensated. Beyond life support measures, therapeutic modalities of upper gastrointestinal bleeding rely on both endoscopic and pharmacological interventions. Tranexamic acid (TA) is an antifibrinolytic that may help control the bleeding in this setting, as it showed an unquestionable benefit in other indications. TA has previously been studied in both upper gastrointestinal haemorrhage from any causes and in liver transplantation of cirrhotic patients. However, there is a lack of data to conclude on its effectiveness (or efficiency) in the early treatment of acute bleeding in cirrhotic patients. Investigators hypothesize that, when given early, TA would be beneficial for cirrhotic patients presenting with acute upper gastrointestinal haemorrhage , by controlling the haemorrhage, avoiding rebleeding episodes and reducing mortality within 5 days after its administration. Moreover, TA could prevent early cirrhosis complications (such as hepatic encephalopathy, sepsis and ascites liquid infection, hepatorenal syndrome), could reduce indications to transjugular portosystemic shunt (TIPS), shorten the length of stay in intensive care unit and the length of hospitalization, and decrease late relapses and one-year mortality.

Conditions

Upper Digestive Bleeding; Cirrhosis

Keywords

Upper digestive bleeding; Haemorrhage; Cirrhosis; Antifibrinolytic; Tranexamic acid; Emergency

Outcome Measures

Primary Outcomes (1)

• The main outcome is a composite criterion and includes: control on acute bleeding, absence of re-bleeding episodes at day 5 and absence of death at day 5 (modified by amendment 1)

  Specifically, the composite criterion is defined by all the following criteria: * Immediate control of the hemorrhage after initial patient management using splanchnic vasoconstrictors and/or proton pump inhibitors, potentially including volume expander, transfusion and/or prescription of vasopressor amines : * Achievement of the transfusion target (Hb ≥ 7 g/dL) 24 hours after initial patient management and then until day 5 * Absence of initiation or increase in vasopressor amines, until day 5 * Absence of recourse to the transfusion of 2 or more red cells packs within 24h to maintain the transfusion target (Hb ≥ 7 g/dL) * Absence of persistence or evolution towards haemorrhagic shock (systolic blood pressure \< 100 mmHg and/or mean arterial pressure \< 60 mmHg and/or heart rate \> 100 bpm) * Absence of re-bleeding episodes at day 5, assessed by the medical team on the bases of clinical, biological or endoscopic elements * Absence of death at day 5

  5 days after randomisation

Secondary Outcomes (15)

• Control of the bleeding

  Within 5 days after randomisation

• Re-bleeding episodes

  At day 6, day 28, day 42, 3 months, 6 months and 1 year after randomisation

• Death

  At day 6, day 28, day 42, 3 months, 6 months and 1 year after randomisation

• Fluid infusion volume (in mL)

  At day 6, day 28 and day 42 after randomisation

• Blood transfusion volume (in mL)

  At day 6, day 28 and day 42 after randomisation

Study Arms (2)

Tranexamic acid

ACTIVE COMPARATOR

At randomisation : loading dose of 1g of intravenous tranexamic acid for 10 min, immediately followed by an intravenous infusion of 3g of TA over 24h

Drug: Tranexamic acid

Placebo

PLACEBO COMPARATOR

At randomisation : loading dose of 10 mL of intravenous isotonic saline for 10 min, immediately followed by an intravenous infusion of 30 mL of isotonic saline over 24h

Drug: Placebo

Interventions

Tranexamic acid DRUG

At randomisation : loading dose of 1g of intravenous tranexamic acid for 10 min, immediately followed by an intravenous infusion of 3g of TA over 24h. Total dose : 4 g of TA

Tranexamic acid

Placebo DRUG

At randomisation : loading dose of 10 mL of intravenous isotonic saline for 10 min, immediately followed by an intravenous infusion of 30 mL of isotonic saline over 24h Total dose : 40 mL of Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Patient treated by a prehospital physician-staffed SMUR team, a firefighter physician-staffed ambulance (ARBSPP), an hospital EMS or an ICU
• Acute upper digestive bleeding (\< 24h) in the shape of hematemesis, described either by the physician, the patient, a relative or a member of the medical team
• Known or suspected cirrhosis (based on clinical/biological/radiographic/anamnestic data)
• Affiliated or recipient of the French social security
• Written consent (or under emergency procedures)

You may not qualify if:

• Known ongoing pregnancy or breastfeeding
• TA already given (if inter-hospital transfer)
• Endoscopy already performed for the current haemorrhagic episode
• Hospitalization for over 24h in an intensive care unit or a routine care unit
• Exclusive lower digestive bleeding or melena only
• Patient in cardiac arrest at the arrival of the prehospital medical team, whether recovered or not
• Patient already randomised once in EXARHOSE study
• TA Counter-indications
• creatininemia \> 500 μmol/L or documented clearance \< 30 mL/min
• documented ongoing CIVD (prior to UDB)
• ongoing seizures
• ongoing arterial or venous thrombosis
• allergy
• Known participation of the patient to another therapeutic study
• Known linguistic inability of the patient to understand the study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

Jean Verdier Hospital

Bondy, 93140, France

RECRUITING

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Marc Jacquet Hospital

Melun, 77000, France

RECRUITING

Related Publications (2)

• Heidet M, Amathieu R, Audureau E, Augusto O, Nicolazo de Barmon V, Rialland A, Schmitz D, Pierrang F, Marty J, Chollet-Xemard C, Thirion O, Jacob L. Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study). BMJ Open. 2018 Aug 10;8(8):e021943. doi: 10.1136/bmjopen-2018-021943.

  PMID: 30099397 DERIVED

• Heidet M, Mermet E, Vaux J, Jeremie R, Audureau E, Marty J. Simulated EMS response times until patients located in public train stations: A geospatial model to improve on-foot accessibility. Resuscitation. 2018 Oct;131:e3-e5. doi: 10.1016/j.resuscitation.2018.07.031. Epub 2018 Aug 2. No abstract available.

  PMID: 30077741 DERIVED

MeSH Terms

Conditions

Fibrosis; Hemorrhage; Emergencies

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Matthieu HEIDET

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthieu HEIDET, MD

CONTACT

matthieu.heidet@aphp.fr

Roland AMATHIEU, MD

CONTACT

roland.amathieu@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2016
• First Posted: January 18, 2017
• Study Start: April 3, 2017
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2020
• Last Updated: April 11, 2018

Record last verified: 2018-04

Locations

FR (3)